Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): study protocol for a two-factorial randomized controlled multi-arm trial with cluster sampling

Background: To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. Methods: This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals' self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Discussion: Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures. Trial registration: ClinicalTrials.gov DRKS00023271. Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien

Physics searches at the LHC

With the LHC up and running, the focus of experimental and theoretical high energy physics will soon turn to an interpretation of LHC data in terms of the physics of electroweak symmetry breaking and the TeV scale. We present here a broad review of models for new TeV-scale physics and their LHC signatures. In addition, we discuss possible new physics signatures and describe how they can be linked to specific models of physics beyond the Standard Model. Finally, we illustrate how the LHC era could culminate in a detailed understanding of the underlying principles of TeV-scale physics.Comment: 184 pages, 55 figures, 14 tables, hundreds of references; scientific feedback is welcome and encouraged. v2: text, references and Overview Table added; feedback still welcom

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Recognizing Proper Tree-Graphs

We investigate the parameterized complexity of the recognition problem for the proper H-graphs. The H-graphs are the intersection graphs of connected subgraphs of a subdivision of a multigraph H, and the properness means that the containment relationship between the representations of the vertices is forbidden. The class of H-graphs was introduced as a natural (parameterized) generalization of interval and circular-arc graphs by Biró, Hujter, and Tuza in 1992, and the proper H-graphs were introduced by Chaplick et al. in WADS 2019 as a generalization of proper interval and circular-arc graphs. For these graph classes, H may be seen as a structural parameter reflecting the distance of a graph to a (proper) interval graph, and as such gained attention as a structural parameter in the design of efficient algorithms. We show the following results. - For a tree T with t nodes, it can be decided in 2^{(t² log t)} ⋅ n³ time, whether an n-vertex graph G is a proper T-graph. For yes-instances, our algorithm outputs a proper T-representation. This proves that the recognition problem for proper H-graphs, where H required to be a tree, is fixed-parameter tractable when parameterized by the size of T. Previously only NP-completeness was known. - Contrasting to the first result, we prove that if H is not constrained to be a tree, then the recognition problem becomes much harder. Namely, we show that there is a multigraph H with 4 vertices and 5 edges such that it is NP-complete to decide whether G is a proper H-graph

Recognizing Proper Tree-Graphs

We investigate the parameterized complexity of the recognition problem for the proper H-graphs. The H-graphs are the intersection graphs of connected subgraphs of a subdivision of a multigraph H, and the properness means that the containment relationship between the representations of the vertices is forbidden. The class of H-graphs was introduced as a natural (parameterized) generalization of interval and circular-arc graphs by Biró, Hujter, and Tuza in 1992, and the proper H-graphs were introduced by Chaplick et al. in WADS 2019 as a generalization of proper interval and circular-arc graphs. For these graph classes, H may be seen as a structural parameter reflecting the distance of a graph to a (proper) interval graph, and as such gained attention as a structural parameter in the design of efficient algorithms. We show the following results. - For a tree T with t nodes, it can be decided in 2^{(t² log t)} ⋅ n³ time, whether an n-vertex graph G is a proper T-graph. For yes-instances, our algorithm outputs a proper T-representation. This proves that the recognition problem for proper H-graphs, where H required to be a tree, is fixed-parameter tractable when parameterized by the size of T. Previously only NP-completeness was known. - Contrasting to the first result, we prove that if H is not constrained to be a tree, then the recognition problem becomes much harder. Namely, we show that there is a multigraph H with 4 vertices and 5 edges such that it is NP-complete to decide whether G is a proper H-graph.publishedVersio